Longitudinal Analysis of the Burden of Post-Acute Chikungunya-Associated Arthralgia in Children and Adults: A Prospective Cohort Study in Managua, Nicaragua (2014-2019).

Chikungunya can result in debilitating arthralgia, often presenting as acute, self-limited pain, but occasionally manifesting chronically. Little is known about differences in chikungunya-associated arthralgia comparing children to adults over time. To characterize long-term chikungunya-associated arthralgia, we recruited 770 patients (105 0-4 year olds [y/o], 200 5-9 y/o, 307 10-15 y/o, and 158 16+ y/o) with symptomatic chikungunya virus infections in Managua, Nicaragua, during two chikungunya epidemics (2014-2015). Participants were assessed at [~]15 days and 1, 3, 6, 12, and 18 months post-fever onset. Following clinical guidelines, we defined participants by their last reported instance of arthralgia as acute (<10 days post-fever onset), interim (>10 and <90 days), or chronic (>90 days) cases. We observed a high prevalence of arthralgia (80-95%) across all ages over the study period. Overall, the odds of acute arthralgia increased in an age-dependent manner, with the lowest odds of arthralgia in the 0-4 y/o group (odds ratio [OR]: 0.27, 95% confidence interval [CI]: 0.14-0.51) and the highest odds of arthralgia in the 16+ y/o participants (OR: 4.91, 95% CI: 1.42-30.95) relative to 10-15 y/o participants. Females had a higher odds of acute arthralgia than males (OR: 1.63, 95% CI: 1.01-2.65) across all ages. We found that 23-36% of pediatric and 53% of adult participants reported an instance of post-acute arthralgia. Children exhibited the highest prevalence of post-acute polyarthralgia in their legs, followed by the hands and torso - a pattern not seen among adult participants. Further, we observed pediatric chikungunya presenting in two distinct phases: the acute phase and the associated interim and chronic phases. Differences in the presentation of arthralgia were observed across age, sex, and disease phase in this longitudinal chikungunya cohort. Our results elucidate the long-term burden of chikungunya-associated arthralgia among pediatric and adult populations. Author SummaryUpon its emergence in the Americas in 2013, chikungunya virus spread rapidly, leading to >2 million suspected autochthonous cases between 2014-2015. Much of what we know about chikungunya is derived from adult populations, leading to gaps in guidelines to treat pediatric chikungunya. To address these gaps, we assembled a large cohort of both pediatric (n=612) and adult (n=158) laboratory-confirmed (n=682) or clinically/epidemiologically probable (n=88) chikungunya cases from two distinct epidemics in 2014 and 2015 in Managua, Nicaragua, followed these patients over a two-year timeline, and analyzed chikungunya-associated arthralgia using rigorous statistical approaches. Our analysis demonstrates that the pediatric (0-15 years old [y/o]) population faces a previously unappreciated high burden of post-acute chikungunya-associated arthralgia. Further, we observe post-acute arthralgia presents differently between pediatric and adult cases (16+ y/o). The difference between the two groups was evident when comparing distribution of polyarthralgia across the body parts and when analyzing the persistence of arthralgia in the post-acute phase (> 10 days post-fever onset). Using detailed longitudinal data, our findings provide insight into long-term chikungunya arthralgia across age, sex, body parts, and the different stages of chikungunya. We believe these findings will inform clinical guidelines regarding chikungunya-associated arthralgia across all ages.